A Single-use Strategy to Enable Manufacturing of Affordable Biologics

Abstract

The current processing paradigm of large manufacturing facilities dedicated to single product production is no longer an effective approach for best manufacturing practices. Increasing competition for new indications and the launch of biosimilars for the monoclonal antibody market have put pressure on manufacturers to produce at lower cost. Single-use technologies and continuous upstream processes have proven to be cost-efficient options to increase biomass production but as of today the adoption has been only minimal for the purification operations, partly due to concerns related to cost and scale-up. This review summarizes how a single-use holistic process and facility strategy can overcome scale limitations and enable cost-efficient manufacturing to support the growing demand for affordable biologics. Technologies enabling high productivity, right-sized, small footprint, continuous, and automated upstream and downstream operations are evaluated in order to propose a concept for the flexible facility of the future.

Keywords: Affinity membrane chromatography; Antibody manufacturing paradigms; B&E, bind and elute; CapEx, capital expense; CoG, cost of goods; Continuous bioprocessing; DSP, downstream process; EBA, expanded bed adsorption; EMA, European Medicines Agency; FDA, Food and Drug Administration; FT, flow through; Flexible, single-use facilities; HCP, host cell protein; MV, membrane volume; OpEx, operating expense; PAT, process analytical technology; Process economics; SMB, simulated moving bed; USP, upstream process; cGMP, current good manufacturing practice.

Fig. 1

Univercells-Natrix automated, integrated, quasi-continuous mAb process concept. The continuous perfusion bioreactor and state-of-the-art DSP techniques are combined for optimum productivity in a small, contained operation.

Fig. 2

Univercells' modular concept for combining USP and DSP in a small-footprint cabinet. The output from the high-productivity perfusion bioreactor (in the left chamber) is continuously feeding into the purification train (in the right chamber). The size and productivity of the perfusion bioreactor is matched with the downstream recovery process for efficient biologic manufacturing.

Fig. 3

Rapid multi-cycling enables small-footprint DSP to match the throughput of high-productivity USP. The conceptual process projected from lab scale proof of concept demonstrates a purification train that is capable of keeping pace with the perfusion bioreactor output. The process is made up of Natrix membrane columns (Protein A, HD-Sb (CEX) and HD-Q (AEX)) that are sized just right for productivity, economy, and flexibility.